Expansion of mixed immune cells using CD3/CD161 co-stimulation for the treatment of cancer

• Published in: Scientific reports Vol. 13; no. 1; p. 6803
• Main Authors: Tsumura, Ryo, Haruta, Miwa, Kuwano, Masataka, Yasunaga, Masahiro
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 26.04.2023; Nature Publishing Group UK; Nature Portfolio
• Subjects: Cancer; CD11c antigen; CD1d antigen; CD3 antigen; CD3 Complex; CD4 antigen; CD56 antigen; CD8 antigen; CD8-Positive T-Lymphocytes; Cell culture; Cytotoxicity; Dendritic cells; Granzyme B; Humans; Immunotherapy; Killer Cells, Natural; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; Natural killer cells; Natural Killer T-Cells; Neoplasms - metabolism; Neoplasms - therapy; NK Cell Lectin-Like Receptor Subfamily B - metabolism; Peripheral blood mononuclear cells; T-Lymphocytes, Cytotoxic - metabolism; Tumor cell lines; Tumor cells; Tumor necrosis factor-α; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-33987-2

Adoptive cell transfer (ACT) is a type of personalized immunotherapy in which expanded immune cells are administered to patients with cancer. However, single-cell populations, such as killer T cells, dendritic cells, natural killer (NK) cells, and NKT (NKT) cells, have been generally used, and their effectiveness remains limited. Here, we established a novel culture method via CD3/CD161 co-stimulation and successfully expanded CD3 /CD4 helper T cells, CD3 /CD8 cytotoxic T cells (CTLs), CD3 /CD56 NK cells, CD3 /CD1d NKT cells, CD3 /CD56 NKT cells, CD3 /TCRγδ T cells, and CD3 /CD11c /HLA-DR dendritic cells in peripheral blood mononuclear cells from healthy donors; their respective numbers were 155.5, 1132.5, 5.7, 117.0, 659.2, 325.6, and 6.8 times higher than those before expansion. These mixed immune cells showed strong cytotoxicity against cancer cell lines Capan-1 and SW480. Moreover, both CD3 /CD8 CTLs and CD3 /CD56 NKT cells killed tumor cells in cell contact-dependent and -independent manners via granzyme B and interferon-γ/TNF-α, respectively. Furthermore, the cytotoxicity of the mixed cells was significantly superior to that of CTLs or NKTs alone. A bet-hedging CTL-NKT circuitry is one potential mechanism underlying this cooperative cytotoxicity. Collectively, CD3/CD161 co-stimulation may be a promising culture method to expand multiple, distinct immune cell populations for the treatment of cancer.